Different classes of neuronal receptors and neurotransmitters in the brain have been implicated in the complex mechanisms underlying the compulsive drinking of alcohol. Experimental findings have favoured the opioid, dopaminergic, serotonergic, and benzodiazepine receptor subtypes. Whether the receptor category is pre- or postsynaptic in nature and whether neurotransmitter synthesis and/or release is equally involved in the manifestation of alcohol drinking is presently unknown.
Drug dependency is extremely difficult to escape. This is true whether the dependency is one based on ethanol, amphetamine, barbituates, benzodiazepines, cocaine, nicotine, opioids, and phencyclidine or the like. Despite active research, there are as yet no drugs that specifically can antagonize for example the alcohol craving in alcohol-dependent subjects. Previous research demonstrated that for example serotonin uptake blockers (e.g. zimelidine, sertraline) reduce voluntary alcohol consumption in rats and humans. However, the mechanism of action of these compounds is not Well understood. There is considerable experimental evidence that the effects on alcohol intake may be an expression of a more general inhibiting role that serotonin plays in consummatory behaviour. Indeed serotonin uptake blockers and serotonin agonists have been shown to reduce a number of oral consummatory behaviours such as the intake of food as well as a variety of flavoured fluids such as alcohol.
The serotonin uptake blocker sertraline, has been found to reduce alcohol intake in rats. Concurrent with the effect on alcohol drinking, however, sertraline lowered the intake of food and water and caused an overall decline in body weights Gill K. et al., Alcohol 5:355-358, 1988; Myers R. D. and Quarfordt S. D., Pharmacol. Biochem. Behav. 40:923-28, 1991). Clearly, it is likely that the action of sertraline on alcohol intake is related to a serotonin uptake blocker's effect on oral consummatory behaviour. Hence, a decline also in the drinking of alcohol would not be unexpected. Furthermore, during the period following the sertraline treatment, the intake of alcohol rose toward the pretreatment level. There is accordingly a need for a more specific and effective agent to be used for treating abuse disorders.